OP0017 RECAPTURE RATES WITH IXEKIZUMAB AFTER WITHDRAWAL OF THERAPY IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: RESULTS AT WEEK 104 FROM A RANDOMIZED PLACEBO-CONTROLLED WITHDRAWAL STUDY
Authors: R. B. M. Landewé, D. Poddubnyy, P. Rahman, R. Bolce, S. Liu Leage, J. Lisse, A. Leung, S. Y. Park, L. S. Gensler
Journal: Annals of the Rheumatic Diseases (2022)

Background COAST-Y is the first study to evaluate the effect of continuing vs withdrawing an IL-17A antagonist, Ixekizumab (IXE) on the maintenance of disease control in patients (pts) with ankylosing spondylitis and non-radiographic axial spondyloarthritis through 104 Weeks (wks). Objectives Here, we describe the final results of pts re-randomized to either placebo (PBO; IXE Withdrawal) or IXE, who experienced flare, and recaptured response before or after open label retreatment during COAST-Y. Methods COAST-Y ( NCT03129100 ) is a Phase 3, long-term extension study that included a double-blind, PBO-controlled, randomized withdrawal-retreatment period (RWP). Eligible pts who completed an originating study (COAST-V, -W, or -X) entered a 24-Week (Wk) lead-in period and received 80 mg IXE every 2 (Q2W) or 4 wks (Q4W) (the treatment regimen at the end of the originating study); pts receiving PBO at the end of COAST-X were assigned to IXE Q4W in COAST-Y. Pts who achieved remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) &lt;1.3 (inactive disease; ID) at least once at Wk 16 or 20, and &lt;2.1 (low disease activity; LDA) at both visits) were randomized 2:1 at Wk 24 to continue IXE (as per lead-in period) or withdrawn to PBO. Pts who subsequently experienced flare (ASDAS ≥2.1 at 2 consecutive visits or ASDAS &gt;3.5 at any visit) were switched to open label IXE Q2W or Q4W at the next visit (same as lead-in period). Time to first flare was analyzed using the Kaplan-Meier method with treatment comparison performed using log-rank test. The observed proportion of pts who recaptured ASDAS LDA and ID were summarized for pts who experienced flare and were retreated with open label IXE. Results A total of 155 pts met the criteria for remission and entered the RWP (PBO [IXE withdrawal], N=53; IXE Q4W, N=48; IXE Q2W, N=54) and 138 completed Wk 104. At Wk 104, significantly more pts in the combined IXE group (75.5%, p&lt;0.001, IXE Q4W: 75.0%, p&lt;0.001; IXE Q2W: 75.9%, p&lt;0.001) remained flare free through Wk 104 vs PBO (Figure 1). Notably, 35.8% of pts on PBO (IXE Withdrawal) never experienced flare. Of the PBO pts who experienced flare and were retreated during Wk 24-104 (N=28), 4 recaptured LDA before switching to open label IXE retreatment, while 23 recaptured LDA and 19 met ID after switching (Table 1). Of the continuously treated IXE pts (N=13), 7 recaptured LDA before switching to open label IXE retreatment, while 5 recaptured LDA and 4 met ID after. Figure 1. The proportion (%) of patients who remained flare free through 104 weeks. ‡p&lt;0.001, †p&lt;0.01, *p&lt;0.05 vs PBO (IXE Withdrawal). Table 1. Recapture of first treatment response before or after switching to open label IXE through 104 weeks among placebo (ixekizumab withdrawal)-treated patients who experienced a flare and retreated Total patients who flared and were switched to open-label ixekizumab retreatment Placebo (ixekizumab withdrawal ) (N=28 ) ASDAS disease activity status LDA ID Recaptured response before open label ixekizumab retreatment 4 1 Recaptured response with open label ixekizumab retreatment (≤16 weeks) 23 14 Recaptured response with open label ixekizumab retreatment (&gt;16 weeks) 0 5 Total patients who recaptured response at week 104 27/28 (96%) 20/28 (71%) Data are presented as n, (%) for the total row and n only for all other rows. In each column, the denominator is 28. ASDAS, Ankylosing Spondylitis Disease Activity Score; ID, inactive disease; LDA, low disease activity including ID; N, number of patients in the analysis population. Conclusion Pts continuously treated with IXE were less likely to experience flare vs pts on PBO (IXE withdrawal). The vast majority of pts withdrawn from IXE to PBO recaptured at least LDA and over half met ID with IXE retreatment. This may provide support for pts who require interruption in therapy. Acknowledgements This study was sponsored by Eli Lilly and Company. Medical writing services were provided by Edel Hughes, PhD and Sumeet Sood, PhD of Eli Lilly and Company, and was funded by Eli Lilly and Company. Disclosure of Interests Robert B.M. Landewé Consultant of: Rheumatology Consultancy BV, AbbVie, UCB, Pfizer, Eli Lilly and Company, Novartis, and Celgene, Denis Poddubnyy Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, and UCB Pharma, Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly and Company, Merck Sharp &amp; Dohme, Novartis, and Pfizer, Proton Rahman Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, and UCB, Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ann Leung: None declared, So Young Park Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly and Company, Grant/research support from: Novartis, Pfizer, and UCB.